活性化された転写複合体Pol II-DSIF-PAF-SPT6の構造
Seychelle M Vos1, Lucas Farnung1, Marc Boehning1
1Max Planck Institute for Biophysical Chemistry, Department of Molecular Biology, Göttingen, Germany.
Nature
|August 24, 2018
まとめ
遺伝子調節にはRNAポリメラーゼII (Pol II) の一時放出が含まれています. 陽性転写延長因子b (P-TEFb) およびSPT6のような他の因子は,抑制因子を置換することによってPol II延長を活性化します.
科学分野:
- 分子生物学
- 遺伝子規制
- 構造生物学
背景:
- 遺伝子調節はRNAポリメラーゼII (Pol II) の活性化に依存する.
- Pol IIの休止はDRB感受性誘導因子 (DSIF) と負の伸縮因子 (NELF) のようなタンパク質複合体によって媒介される.
研究 の 目的:
- Pol IIの一時解離と延長活性化の分子メカニズムを解明する.
- 構造的な基礎を定めるために,一時停止から活性化された延長複合体への移行.
主な方法:
- 複合体の形成と機能を研究する in vitro 生化学的測定法.
- 高解像度構造を決定するための冷凍電子顕微鏡 (冷凍EM).
- 休止と活性化された延長複合体の比較構造分析.
主要な成果:
- 活性化されたPol II延長複合体の形成には,正の転写延長因子b (P-TEFb),PAF1複合体 (PAF),およびSPT6が必要です.
- Cryo-EMは3.1 Åの解像度で活性化された複合体の構造を明らかにした.
- PAFはNELFを位移し,P-TEFbはPol IIをリン酸化し,SPT6はリン酸化C末端領域と相互作用し,DSIFRNAクランプを開きます.
結論:
- この研究は,Pol IIの休止がどのように放出され,延長が活性化されるかについての分子理解を提供します.
- 構造的な洞察は,トランスクリプションの延長を促進する重要な要因の役割を明らかにします.
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